Semi-automatic coating system apparatus

ABSTRACT

A semi-automated coating system for providing medical devices with antimicrobial coatings is disclosed. The semi-automated coating system extends the coating solution&#39;s usable life span by minimizing exposure to light, air and temperature extremes. Moreover, the disclosed semi-automated coating system minimizes operator and environmental exposure to the coating solutions. Methods disclose techniques for preparing coating solutions, setting up the coating system and operating the device. Moreover, the systems and methods described herein minimize operator intervention with the coating processes and provide superior product consistency.

This application is a National Stage under 35 USC 371 of InternationalPatent Application No. PCT/US01/23699, filed Jul. 30, 2001,SEMI-AUTOMATIC COATING SYSTEM AND METHODS FOR COATING MEDICAL DEVICES.This application is a division of and claims the benefit of U.S. patentapplication Ser. No. 09/630,175, filed Aug. 1, 2000, now U.S. Pat. No.6,534,112, entitled “SEMI-AUTOMATIC COATING SYSTEM METHODS FOR COATINGMEDICAL DEVICES”.

FIELD OF THE INVENTION

The present invention generally relates to methods and systems forcoating medical devices. Specifically, the present invention relates tosystems and methods for automating batch processing of medical devicesin a closed system. More specifically, the present invention providessemi-automated methods and systems for coating implantable medicaldevices with antimicrobials using closed systems that maintain coatingsolution integrity, increase product throughput and minimizes personneland environmental exposure to the coating solution.

BACKGROUND OF THE INVENTION

Localized and systemic infections represent one of the most serious postsurgical complications. Over the past fifty years tremendous advances inmaterials, training and antimicrobial therapies have significantlyreduced the number of life-threatening post operative infections. Thedevelopment of pre-sterilized disposable surgical dressings, medicalinstruments, gowns, drapes and other materials have helped reduceinfection frequency. However, the development of improved antimicrobialsrepresents the single most significant advance in infection control.

There are essentially three categories of antimicrobial agents:antiseptics, disinfectants and antibiotics. Antiseptics are generallydefined as compounds that kill or inhibit the growth of microorganismson skin or living tissue. Antiseptics include, but are not limited to,alcohols, chlorhexidine, iodophors and dilute hydrogen peroxide.Disinfectants are compounds that eliminate pathogenic microorganismsfrom inanimate surfaces and are generally more toxic, and hence moreeffective, than antiseptics. Representative disinfectants include, butare not limited to, formaldehyde, quaternary ammonium compounds,phenolics, bleach and concentrated hydrogen peroxide. Antibiotics arecompounds that can be administered systematically to living hosts andexhibit selected toxicity, that is, they interfere with selectedbiochemical pathways of microorganisms at concentrations that do notharm the host. In the alternative, an ideal antibiotic will targetspecific metabolic pathways that are essential for the parasite, butabsent in the host. Antibiotics generally work using one of four basicmechanisms of action: 1) inhibition of protein synthesis; 2) inhibitionof cell wall synthesis; 3) interference with nucleic acid synthesis; and4) altering cell membrane selective permeability. Antibiotics include,but are not limited to penicillins, aminoglycosides, tertacyclines andmacrolides,

The fundamental difference between antiseptics, disinfects andantibiotics is the ability of microorganisms to develop resistance toantibiotics. The characteristics that make antiseptics and disinfectantsso effective generally precludes the development of resistantmicroorganisms. However, disinfectants are unsuitable for use on livingtissues and many antiseptics are primarily limited to localized,generally topical, applications. Consequently, most antimicrobialprophylactic and therapeutic regimens rely on antibiotics.

The microorganism's susceptibility to an antimicrobial and the abilityof the antimicrobial to reach the infection site are the two mostsignificant factors that determine antimicrobial therapy efficacy.Antimicrobial susceptibility is generally determined by culturing theorganism in the laboratory and testing it against a panel of candidatedrugs. However, laboratory testing can only be done if the agent causingthe infection is known. When antibiotics are used prophylactically, asis the case with surgical patients, physicians generally prescribe drugstargeted to suppress the growth of the most common post surgicalinfectious agents. One of the most common organisms associated withsurgical infections is Staphylococcus aureus. In the past, penicillinclass drugs were considered the drugs of choice to thwart S. aureusinfections. However, recently, many new antibiotic resistantmicroorganisms including penicillin resistant S. aureus have emergedmaking post surgical infection control even more challenging.Consequently, physicians have turned to new generations of antibioticsin response to emerging resistant strains.

Until recently, methicillin, an analogue of penicillin, was thepreferred drug for treating and preventing penicillin resistant S.aureus infections. However, methicillin resistant S. aureus (MRSA) arebecoming increasingly more common. Therefore, newer and more effectivetreatments for MRSA as well as other difficult to treat post surgicalinfections are in great demand.

One approach to treating and preventing the emergence of antibioticresistant bacteria such as MRSA is to use two or more antimicrobialcompounds in combination. The advantages to this approach include havinga second antimicrobial present to inhibit resistant sub-populationemergence during treatment and the potential for antimicrobial synergy.Antimicrobial synergy occurs when the efficacy of one antimicrobial isenhanced by another such that the total antimicrobial effect is greaterthan either one alone. In many cases either antimicrobial usedseparately may not completely eradicate the infection, but when thedrugs are used in combination, powerfully efficacious antimicrobialregimens result.

However, even the most sensitive microorganisms cannot be killed byantimicrobials unless they can reach the infection site (antimicrobialbioavaliablity). Numerous factors determine antimicrobial bioavailablityincluding route of administration, clearance rates from the body, tissuesolubility, and the degree of blood flow surrounding the infected site.Antimicrobials that are susceptible to destruction by digestive fluids,or drugs not easily absorbed in the intestines, must be administerparenterally (usually intravenously). However, regardless of theadministration route, the antibiotic must survive circulation throughthe blood stream prior to reaching the treatment site. If the liver orkidneys rapidly removes an antimicrobial from the blood stream, or ifthe antimicrobial has a high affinity for blood proteins such that it isbound and inactivated by the blood, its bioavailability can besignificantly reduced. This is especially true if the infection site isdeep within tissues or organs that have minimal blood flow.

Deep tissue infections can result when medical implants becomecontaminated prior to surgical placement. When oral or parenterallyadministered antimicrobials fail to effectively control and eliminatethe infection, the medical implant may have to be removed. Removalrequires additional surgical procedures to treat the infection andre-implant the device after the infection completely resolves. Moreover,once deep tissue infections are established, long term antimicrobialtherapy and hospitalization may be required. These additional proceduresincrease the costs associated with device implantation, subject thepatient to discomfort and in rare circumstances, increase the threat ofpermanent disfigurement.

Coating implantable medical devices with antimicrobial compoundsprovides a technique for deep tissue drug delivery that cansignificantly reduce the risk of post implantation infections. Coatingprocedures should employ broad spectrum antimicrobials that areeffective against most post surgical infections, especially MRSAinfections. The antimicrobials need to be soluble in physiologicalfluids and must be stable enough to survive processing steps required tosuccessfully coat the medical device. Ideally, a synergisticantimicrobial combination should be used. Non-limiting examples ofantimicrobial combinations are described in U.S. Pat. Nos. 5,624,704 and5,902,283, the entire contents of which are herein incorporated byreference. Moreover, the antimicrobial coating procedure must employmethods and materials that are compatible with the antimicrobial and thematerial used to make the medical device. Medical devices, specificallyimplantable types, can be fabricated from a wide variety ofbiocompatible compounds including metals and polymers. Each materialpresents its own unique challenges to material scientists when it isnecessary, or desirable, to coat medical devices with bioactivematerials. However, all coating methodologies share common objectivesincluding the need to maximize expensive and labile coating solutions,minimize environmental contamination, provide the medical device with aneven coating, and maintain an efficient, controlled process thatcomplies with Federal Food and Drug Administration (FDA) GoodManufacturing Practices (GMP). Tedious manual methods of batch coatingmedical devices cannot achieve these goals for all medical devices on aconsistent basis.

The size, shape and composition of the medical devices can significantlylimit manual methods. Moreover, lot-to-lot consistency, GMP complianceand product throughput are all greatly enhanced when automated, orsemi-automated, processes are involved. Moreover, non-automatedprocesses subject expensive coating solutions to contamination andexcessive waste resulting from spillage and product handling.Additionally, many polymeric compounds used to make medical devices arecoated using harsh and often toxic solvent mixtures in order to imbibethe coating material into the devices. Exposure to these solvents posesa potential risk to personal, equipment and the environment that can bebest minimized by coating in a closed system, a process incompatiblewith most manual methods.

Therefore, there is a need for methods and systems that can provideimplantable medical devices with antimicrobial coatings. Moreover, thereis a need for methods and systems that can provide antimicrobialcoatings in a closed system that reduce exposure to toxic solvents,maintain coating solution integrity for prolonged periods, allow formaximum product throughput, provide the medical device with aconsistent, even coating, minimize product handling and accomplishesthese goals in an FDA GMP compliant manner.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a self-contained,automated system for coating a medical device with a antimicrobials.

It is another object of the present invention to provide antimicrobialcoating systems and methods that extend the usable life expectancy (potlife) of the coating solution by limiting the solution's exposure toatmospheric conditions including light and air.

It is still another object of the present invention to provideantimicrobial coating systems and methods that extend the pot life ofthe coating solution by minimizing thermal exposure.

It is another object of the present invention to provide antimicrobialcoating systems and methods that protect the operator and theenvironment from the coating solution.

It is yet another object of the present invention to provideantimicrobial coating systems and methods that are automated andminimize user intervention.

It is another object of the present invention to provide implantablemedical devices having antimicrobial coatings that reduce postimplantation infections by releasing antimicrobial compounds into thesurrounding tissues for sustained time periods.

The coating solutions of the present invention are composed ofantimicrobial compounds including, but not limited to, antiseptics andantibiotics dissolved in potentially toxic organic solvents. Thesesolutions are extremely expensive to prepare and are easily inactivatedby exposure to temperatures above ambient, air (specifically reactiveoxygen species), light (specifically ultraviolet light) andcontamination. Therefore, maximizing the pot life requires precisetemperature control and protection from air, light and contamination.The methods and systems of the present invention accomplish these andother goals and simultaneously reduce the manufacturing environment'sexposure to potentially toxic coating solutions. (It is important todistinguish the coating solutions from coated medical devices. Thecoating solutions of the present invention are highly concentratedmixtures of antimicrobial compounds and solvents. These mixtures may betoxic to manufacturing professionals exposed to large concentrations.However, the coated medical device, when used in accordance with themanufacturer's directions for use and under the supervision of aqualified physician, present minimal or no risks to the patient).

The present invention provides methods and systems that permit medicaldevices to be safely coated with antimicrobial compounds whilemaximizing pot life. However, the systems and methods of the presentinvention can be used to coat any device safely and efficiently with awide range of different compounds and are not limited solely toproviding medical devices with antimicrobial coatings.

The use of the term “coating” is not intended as a limitation andincludes any physical or chemical method of providing the surfaces, orpolymeric matrices, of medical devices with antimicrobial properties.Non-limiting examples of such chemical and physical methods includeimpregnation, imbibing, ionic interactions, covalent bonds, van derWaals forces, hydrogen bonding, protein-protein interactions,antibody-antigen complexes, resin coatings, electrodeposition, plasmadeposition or the like. Hence the term coating is not to be construednarrowly to mean merely a surface layer, but should be interpreted toinclude providing a homogeneous concentration or gradient ofantimicrobials throughout a medical device's body.

The present inventors have determined that optimum coating of medicaldevices occurs when the coating solution is heated to temperatures thatsignificantly accelerate the degradation of the coating solution. Inorder to optimize the coating process and simultaneously maximize thesolution's pot life, the coating solutions of the present invention arepreheated in a holding vessel before being transferred to a processingvessel containing the medical devices. Any coating solution remaining inthe holding vessel is cooled to ambient temperatures or below while theprocessing vessel containing the antimicrobial solution and medicaldevice is held at a constant elevated temperature. At the conclusion ofa predetermined optimum processing time, the coating solution istransferred from the processing vessel back to the holding vessel whereit is cooled to ambient temperatures or below. This entire process isconducted in a sealed system that protects the coating solution fromexposure to damaging environmental factors, reduces solvent evaporationand isolates manufacturing personnel from the solution.

After the medical device has been coated it is aerated for apredetermined time period using a pressurized gas flow (sparging system)and then washed at least once using a wash solution that is pumped intothe closed processing vessel and gently agitated using the spargingsystem of the present invention. After washing is completed, a gas,usually air, is passed over the medical device using the sparger toaccelerate the drying process. The device is then removed from thesealed system and packaged prior to terminal sterilization.

The entire process of the present invention is under the control of aprogrammable microprocessor/controller that receives a series of imputesfrom remotely located sensors. Each sensor monitors an event andcontinually notifies the microprocessor/controller of its status. Shouldany sensor detect an out-of-range condition, the system will either failto initiate the next step or abort the process while simultaneouslynotifying an operator of a default situation.

In one embodiment of the present invention the self-contained coatingsystem is attached to a containment platform to collect and confineaccidental coating solution spills. Attached to the containment platformis at least one temperature controller consisting of either a heater, achiller or a combination thereof, a holding vessel a processing vesseland at least one fluid transfer system. The fluid transfer system movescoating solution between the holding and the processing vessels and/orwash solution to and from the processing vessel. In one embodiment ofthe present invention there are a plurality of fluid transport systemseach directing the flow of different fluids between the holding vesseland processing vessel and/or fluid reservoirs.

In one embodiment of the present invention the holding and processingvessels are fitted with sealable closures and at least one mixing devicefor maintaining uniform antimicrobial solution and for preventingthermal gradients from forming. The processing vessels of the presentinvention are also fitted with a sparging system that provides a gasflow into the processing tank during the aeration, washing and dryingsteps. In one embodiment of the preset invention the gas flow velocitymay be adjusted to optimize the particular process step.

In another embodiment of the present invention the antimicrobial coatingsystem includes one or more valve assemblies located at various pointsalong the fluid transfer systems and gas lines. Additionally, numeroussensors may be located on the holding vessel, the processing vessel,vessel closures, the heat transfer devices, the fluid transfer systems,and temperature controllers. Each sensor feeds information to aprogrammable microprocessor that controls contents, temperatures, fluidlevels, and gas flow within the holding and processing vessels. Theprogrammable microprocessor of the present invention can also be adaptedto open and close valves and act as a fail-safe monitor responsive toremote sensors.

In another embodiment of the present invention a method for coating amedical device is provided. This method includes providing a sealablefirst vessel filled with a coating solution and a sealable second vesselcontaining a medical device to be coated. The coating solution in thefirst vessel is preheated to a temperature appropriate for the coatingprocess and then transferred to the second preheated vessel. Any coatingsolution remaining in the first vessel is cooled to at least ambienttemperature and the coating solution in the second vessel is held at aconstant coating process temperature until the processing interval iscomplete. At the conclusion of the processing interval the coatingsolution in the second vessel is transferred back to the first vesseland cooled.

The coated medical device is then aerated, after which the wash solutionis transferred into the second vessel and the medical device is washedwhile gas is gently sparged into the wash solution. After apredetermined period the wash solution is removed and the wash step isrepeated as many times as desired. After washing is complete the medicaldevice is dried using a higher velocity of sparged gas. The entiremethod can be automated by providing a microprocessor/controllerresponsive to at least one remote sensor.

Other objects and features and advantages of the present invention willbe apparent to those skilled in the art from a consideration of thefollowing detailed description of preferred exemplary embodimentsthereof taken in conjunction with the Figures which will first bebriefly described.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram that depicts the general coating process inaccordance with the teachings of the present invention.

FIG. 2 depicts the basic components of the coating system of the presentinvention.

FIG. 3 depicts one embodiment of a product suspension device used inaccordance with the teachings of the present invention.

FIG. 4 depicts one embodiment of the gas sparger used in accordance withthe teachings of the present invention.

FIG. 5 depicts the control panel of the microprocessor/controller of thepresent invention.

FIG. 6 depicts the compressed gas flow and gas vents used in oneembodiment of the present invention.

FIG. 7 schematically depicts coating solution transfer between theholding vessel and processing vessel in accordance with the teachings ofthe present invention.

DETAILED DESCRIPTION OF THE INVENTION

Deep tissue infections associated with in vivo medical devicesoccasionally occur when a medical device is accidentally contaminatedwith pathogenic or opportunistic microorganisms prior to implantation.Accidental contamination can occur if the integrity of the productpackaging is compromised after terminal sterilization, or if the productcontacts a contaminated surface after being removed from its packagingimmediately prior to implantation. If the contaminated medical device isimplanted, the microorganism may begin to proliferate in the tissuessurrounding the implanted device, resulting in an infection.

Generally, systemic antibiotics are administered prior to surgery andcontinued for an additional seven days or more. However, systemicantibiotics may not always prevent the establishment of deep tissueinfections. For example, an organism will continue to multiply unabatedif it is resistant to the antibiotics being administered, or if theantibiotic does not reach the infection site in concentrations requiredto kill the organism. Recently, temporary medical devices such ascatheters having antimicrobial coatings that are released in effectiveconcentrations for sustained periods have been employed to help preventpost implantation infections. However, the antimicrobial coatingsolutions used are extremely expensive and generally require coatingprocedures that rely on elevated temperatures and toxic solvents inorder to obtain uniform stable coatings.

Standard manufacturing practices rely on batch containing techniquesthat involve manually transferring the coating solutions into processingtanks and heating the solution to process temperature. The medicaldevices are immersed in the heated coating solution for a predeterminedtime and then removed from the processing tank and manually washed. Thecoating solution is maintained at coating temperatures for the durationof the manufacturing shift and then discarded due to antimicrobialthermal breakdown and solvent evaporation. Consequently, largequantities of antimicrobials and solvents are used each time a medicaldevice batch is coated. The cost and waste associated with batchprocessing techniques is easily amortized when thousands of smallmedical devices are coated in a single batch. However, large bulkymedical devices that displace large volumes of coating solution cannotbe economically coated using batch methods. Moreover, large quantitiesof potentially toxic solvents are required to batch coat bulky medicaldevices. This results in increased material and solvent disposal costs,excessive personnel and environmental exposure and reduced productconsistency.

The present invention provides methods and systems that significantlyextend the useable life span of a coating solution (pot life) andfacilitate the safe and efficient processing of large quantities ofmedical devices. The present invention is particularly well adapted toprocessing large quantities of bulky medical devices with increasedeconomy and safety.

The term “coating” used herein is not intended as a limitation and isnot to be construed as a process that merely covers or saturates amedical device's surface. Rather, the term coating is defined as anymethod, chemical or physical, that provides a medical device withantimicrobial properties, including, but not limited to, the medicaldevice's exterior surfaces and/or internal matrices.

The coating solutions of the present invention can be used to providemedical devices with antimicrobial properties utilizing a variety ofphysical and chemical interactions between the device and the coatingmaterials. In one embodiment of the present invention polymericcompounds, such as, but not limited to, silicones, polyolefins andpolyesters can be impregnated with the antimicrobial coatings through animbibing process. Imbibing occurs when a polymer is suspended in asolvent mixture that swells the polymer matrix carrying solutes presentin the solvent into the polymer itself. After the polymer has beenremoved from the solvent the polymer matrix returns to its pre-swollenconfiguration, trapping solute molecules within the polymer. In thepresent invention solute molecules include antiseptics and/orantibiotics. Other physical and chemical processes may be used toprovide homogeneous concentrations or antimicrobial concentrationgradients to medical devices of the present invention. The chemicaland/or physical makeup of the medical device dictates the optimumprocess.

In one embodiment of the present invention antimicrobial compounds aredissolved in organic solvents that swell the polymer causing theantimicrobials to be carried into the polymer matrix, trapping themwithin after the device is removed from the solvent. The presentinventors have determined that this process is particularly valuablewhen providing delicate thin-walled silicone medical devices withantimicrobial coatings. In one embodiment of the present inventionsolvent exposure was limited to approximately 30 minutes at atemperature of approximately 35° C. This process impregnates siliconedevices with effective amounts of antibiotics while preserving theintegrity of the silicone polymer matrix.

The coating system of the present invention is composed of a holdingvessel for storing and preheating the coating solution, a processingvessel for coating, aerating, washing and drying medical devices, afluid transfer system for transporting coating and wash solutionsbetween the vessels and reservoirs, a temperature controller that heatsand cools the solutions, a gas sparging system to facilitate aerating,washing and drying, solution mixers and a microprocessor/controller thatautomates the entire process. In one embodiment of the present inventionthe entire system is coupled to a containment platform that confinesaccidental coating solution spills and prevents contamination of themanufacturing environment with potentially toxic solvents.

The present invention can be used to coat medical devices made from anybiocompatible material including but not limited to metals and syntheticand natural polymers. Non-limiting examples include stainless steel,nickel, titanium, silver, gold, platinum, aluminum and alloys thereof,natural rubber latex, synthetic latexes, silicone, polyolefins, andpolyesters. In one embodiment of the present invention the coatingsolution is composed of solvents including, but not limited to butylacetate, methyl alcohol, amyl acetate, benzene, carbon tetrachloride,chloroform, diethyl ether, ethylene dichloride, hexane, 2-ethyl hexanol,hexyl ether, methyl ethyl ketone (MEK), methyl isobutyl ketone,methylene chloride, perchloroethylene, Stoddard solvent (mineralspirits), toluene, trichloroethylene, xylene and combinations thereof.

The solvent chosen must be compatible with the medical device and theantimicrobial. The antimicrobial must be soluble in the solvent systemselected and not denatured once dissolved. Polyolefin, polyester andsilicone medical devices are generally used with solvent systems thatswell the polymer's surface, permitting the solvent to carry theantimicrobial into the polymer's surface (imbibe). However, the solventshould not destroy the polymer's functional characteristics. After themedical device is removed from the solvent/antimicrobial mixture thedevice is allowed to regain its functional properties during theaeration, washing and drying steps.

In one embodiment of the present invention the medical device iscomposed of silicone and the solvent system is a butyl acetate andmethanol blend. The antimicrobials are first dissolved in the methanoland then the butyl acetate is added; the resulting mixture is used toimbibe the antimicrobial into a silicone medical device. After apredetermine coating interval, the solvent/antimicrobial mixture isremoved and the silicone medical devices of the present invention arewashed then dried. Silicone medical devices are easily softened whenexposed to swelling solvents such as butyl acetate. Immediately afterthe solvent is removed the silicone devices are extremely fragile andcan be easily broken if handled in an aggressive manner.

In one embodiment of the present invention the fragile coated medicaldevices are aerated using sparged gas immediately after the coatingsolution has been returned to the holding vessel, the aeration processcontinues for a predetermined time sufficient to allow structuralintegrity to return to the polymer. At the conclusion of the aerationprocess the medical devices of the present invention are washed.

Wash fluids are added to the processing vessel gently to avoiddisturbing the devices. In one embodiment of the present invention thewashing fluid enters the processing vessel through a port near thevessel top and is deflected downward along the vessel sides. In anotherembodiment of the present invention the wash fluids slowly fill from thevessel's bottom. Washing is facilitated by sparging a low velocity gasstream into the wash fluid via a sparge system located at the vessel'sbase. This low velocity gas sparge gently agitates the wash solution toaid in removing excess antimicrobial deposits that accumulated on theproduct during coating. During the washing process the silicone devicesof the present invention continue to regain firmness and becomeincreasingly resistant to tearing and deformation. Final polymerintegrity is restored as the medical devices are dried in the processingvessel under a stream of sparged gas.

The present inventors have determined that the aeration, washing anddrying processes of the present invention are greatly enhanced when gasis sparged into the processing vessel during these steps. Gas isprovided to the process vessel sparger using either compressed gascylinders or a remote gas compressor. The gas used may be, but is notlimited to, air, nitrogen, argon or other minimally reactive gases orgas mixtures. In one embodiment of the present invention the sparger isa spiral shaped device made from stainless steel or other non-reactivealloys and is sealed to the processing tank's bottom. Gas can be passedthrough the sparger at variable rates controlled by either themicroprocessor/controller of the present invention or manually. In oneembodiment of the present invention the gas is used at one velocityduring aeration and drying steps and a second, lower velocity during thewashing step. The gas is vented to the outside through a series of gaslines connected to a valve located near the vessel top. The ventingmechanism of the present invention may also provide one or morehigh-efficiency particulate air (HEPA)/volatile organic compound (VOC)filtration systems.

The antimicrobial solutions used in accordance with the teaching of thepresent invention are composed of heat labile antimicrobials such as,but not limited to, antibiotics and antiseptics. These labileantimicrobial compounds are extremely expensive and need to be dissolvedin volatile solvents including, but not limited to, water, alcohols,ketones, ethers, esters and aldehydes. When batch-coating techniques areemployed the coating solutions of the present invention are exposed toabove ambient temperature conditions that accelerate the thermalbreakdown of the antimicrobials. Moreover, open, or partially sealed,containers are often used to prepare the solutions and coat the medicaldevices. These containers may expose the coating solution to ultravioletlight and air that further accelerate antimicrobial breakdown andpromote volatile solvent evaporation. As the solvents evaporate and thecompounds deteriorate, the exact concentration of biologically activecoating material changes and the coating solution begins to discolor.Medical devices coated using the deteriorated solutions have unknownbiological activity and are cosmetically unattractive. Consequently, thedeteriorated coating solution must be destroyed and a new solutionprepared before further coating can occur.

In one embodiment of the present invention the coating solution iscontinuously maintained under an inert atmosphere. After theantimicrobial coating solution has been prepared as described in Example1 below, an inert gas, such as, but not limited to, bone-dry nitrogen isinjected into the holding tank such that air present in the holding tankis displaced through a vent located near the holding vessel's top abovethe fluid level.

In another embodiment a sparging apparatus is incorporated into thebottom of the holding vessel through which the inert gas is introduced.Inert gas is also provided to the entire coating system including allgas lines, fluid paths, fluid transfer systems and the processing tank.In this embodiment the entire coating system remains under an inertatmosphere until the system is opened to air. The holding vesselcontaining coating solution is continually maintained in an inertatmosphere and remains sealed until such time as a new batch of coatingsolution is prepared. As the fluid level within the holding vessel isreduced during coating solution transfer to the process vessel, inertgas is pumped into the holding vessel to prevent a partial vacuum fromforming therein. In one embodiment of the present invention inert gasdisplaced from the filling process vessel is transferred to the emptyingholding vessel. In another embodiment inert gas is vented out of thefilling process vessel and inert gas is provided to the emptying holdingvessel from an inert gas reservoir. However, the process of providinginert gas to emptying vessels and removing insert gas from fillingvessels will depend on the coating system configuration and any suchprocesses are considered within the scope of the present invention.Engineers of ordinary skill in the art would be capable of configuring asuitable gas transfer system consistent with the teachings of thepresent invention.

The coating systems and processes of the present invention provideimproved coating solution stability and enhanced operator safety byemploying a sealed, semi-automated system having the capacity tomaintain coating solutions at temperatures that improve stability,reduce evaporation and prevent atmospheric contamination. The coatingsolutions of the present invention are heated to coating temperature fora minimum period and then cooled to holding temperature until the nextcoating cycle is initiated.

Examples of medical devices that can be coated using the systems andmethods of the present invention include, but are not limited to,catheters, surgical slings, artificial joints penial implants, ocularimplants, stents, suture and heart valves.

FIG. 1 depicts the process 100 of the present invention in a generalizedblock diagram. The semi-automated process of the present inventionbegins 101 when the coating solution stored 124 at or below ambienttemperature in the holding vessel is heated to process temperature 102.Product is transferred 104 into the processing vessel and the cycle isinitiated 106 when the coating solution reaches process temperature.Coating solution is pumped 108 into the holding vessel 108 and theproduct is coated for a predetermined time 110. Any coating solutionremaining in the holding vessel is cooled to ambient temperature orbelow. At the conclusion of the coating step the coating solution ispumped back into the holding vessel and cooled 112. The coated productremaining in the processing vessel is aerated 116 to provide time forthe swollen product matrix to reform, and/or for the coating material tofully imbibe. The product is the washed 118 using a wash solution andgentle agitation from sparged gas. At the completion of the wash step120 the wash fluid is drained from the processing vessel and the washstep is repeated 120 a, or the product is removed from the processvessel and dried 122. In another embodiment of the present invention theproduct 121 is dried in the processing vessel.

Turning now to FIG. 2. The coating system of the present invention isgenerally depicted at 200 and is composed of a holding vessel 202 forstoring the coating solution at or below ambient temperature and forpreheating the coating solution to a predetermined process temperature.In one embodiment of the present invention the coating solution ispreheated in the holding vessel 202 using a circulating heater 206. Thecirculation heater 206 cycles a heat transfer fluid through thermaljackets that envelop holding vessel 202 and processing vessel 204.Circulation control valves 208 a and 208 b facilitate heat transferfluid circulation. The coating solution in holding vessel 202 iscontinually mixed using an overhead low shear mixer 210 to prevent theformation of thermal gradients and to keep the coating solution in ahomogenous state.

Holding vessel 202 is fitted with a first sealable closure 212 thatprevents solvent evaporation, minimizes contamination and reducesenvironmental exposure to the coating solution. Product to be coated issuspended in processing vessel 204 using devices and methods known tothose skilled in the art. A non-limiting example of a product suspensiondevice is depicted in FIG. 3 at 300. After the product has been securelyloaded into processing vessel 204, second sealable closure 218 issecured. The proper sealing of closure 218 is detected by the processvessel closure sensor 220 that is in electronic communication withmicroprocessor/controller 216.

The coating cycle is initiated by engaging cycle initiate button 214 onmicroprocessor/controller 216. Microprocessor/control 216 will not allowthe coating process to begin unless inputs from solvent temperaturesensor 222, process vessel closure sensor 220 and process latch sensor224 indicate the coating solution is at processing temperature and theprocess vessels closure 218 is closed and latched. The coating processbegins as pre-heated coating solution is transferred from holding vessel202 by pump/direction valve network 226 into process vessel 204.

The treatment timer 228 is activated when fluid level sensor 230 detectsa level of coating solution sufficient to cover the product. At theinitiation of the treatment period holding vessel 202 is isolated fromcirculation heater 206 and circulation cooler 232 begins circulatingcooled heat transfer fluid through holding vessel's 202 thermal jacket.The coating solution in processing vessel 204 is maintained at coatingtemperature and continually mixed using a magnetically coupled mixer 234located at process vessel's 204 base. Mixing maintains an even elevatedtemperature throughout the coating solution in the processing vessel andremains engaged as long as treatment timer 228 is active.

At the completion of the treatment period, pump/direction valve network226 reverses direction and coating solution in process vessel 204 ispumped back into holding vessel 202. Circulation cooler 232 continuescirculating cooled heat transfer fluid through holding vessel's 202thermal jacket to cool returning coating solution to ambient temperatureor below. After all remaining coating solution is removed fromprocessing vessel 204 an aeration cycle is initiated.

During the aeration cycle gas passes through filter 242 and intoprocessing vessel 204 through sparger (see FIG. 4 at 402) connector toprocess vessel's 204 bottom through gas line 246. The filtered gaspasses over the coated product and out of process vessel 204 through gasline 244. High velocity gas regulator 236 that is responsive tomicroprocessor/controller 216 controls aeration gas flow velocity. Theaeration period is regulated by aeration timer 238 located and under thecontrol of microprocessor/controller 216. At the completion of theaeration cycle microprocessor/controller 216 shuts off the gas flow andengages wash fluid pump system 248 that provides wash fluid from washfluid reservoir 250 to process vessel 204 though fluid supply line 252.

Wash fluid level is monitored by fluid level sensor 230 that isresponsive to microprocessor/controller 216. After the preset wash fluidlevel is reached microprocessor/controller 216 shuts off wash fluidvalve 248 and engages low velocity gas regulator 254. The low velocitygas flows through filter 242 and into processing vessel 204 throughsparger (see FIG. 4 at 402) connector to process vessel's 204 bottomthrough gas line 246.

Wash timer 240 responsive to microprocessor/controller 216 regulates thewash interval. When wash timer 240 times out, microprocessor/controller216 closes vent valve 260 and low velocity gas provided through sparger(see FIG. 4 at 402) pressurizes process vessel 204. Vessel out valve 256and drain valve 258 are opened by the microprocessor/controller 216 andwash fluid exits processing vessel 204. The entire wash procedure can berepeated as many times as desired as herein described. The washedproduct can be removed from process vessel 204 at the completion of thewash step(s), or dried in sealed process vessel 204 using a highvelocity air flow as describe for the aeration step above.

The present invention can be made from any assortment of materialscompatible with the intended solutions and processes. In one embodimentof the present invention the holding vessel 202, processing vessel 204,and all associated metallic components that contact product or thecoating solution are made entirely of stainless steel. Valve seats,seals, and fittings that contact coating solution are composed of, butnot limited to Teflon® and Delrin®, (Teflon® and Delrin® are productsmade by E. I. du Pont de Nemours and Company of Wilmington, Del.).

The inventors of the present invention have determined that sparging gasinto processing vessel 204 during one or more process steps 100 (FIG.1), including, but not limited to post-coating, pre-wash step (aeration)116, the washing process 118 and as an adjunct to drying 121significantly improves coating consistency and appearance. Any number ofgas sources can be used including, but not limited to air, nitrogenhelium, argon or any combination therefore. In one embodiment of thepresent invention compressed air is provided to the coated productsthrough a sparger 402 (FIG. 4) located near the bottom of processingvessel 204. Compressed gas passes through filter 242 having a meanporosity of between approximately 0.1 μm to 10 μm, preferably betweenapproximately 0.5 μm and 2 μm, more preferably 0.7 μm to 1.0 μm, beforeentering sparger 402. The novel spiral shape of sparger 402 provides avortex motion to the air current or wash fluid depending on the processcycle. The present inventors believe that the vortices significantlyincreases the sparger's efficiency and provides for a gentle, butthorough, agitation during the wash cycle.

The valves of the present invention that control the fluid and gas flowcan be electronically or pneumatically activated. In one embodiment ofthe present invention the valves are pneumatically activated Teflon®seated ball valves. In other embodiments of the present inventionelectromechanical valves could be used. However, when potentiallyflammable solvents are used with the coating system of the presentinvention electromechanical valves present the potential for ignitingthe solvents. Consequently, the present inventors have chosen to use themore versatile and generally safer pneumatic activated valves.Electronic solenoid valves isolated in microprocessor/controller 216control the pneumatically activated valves of the present invention.When a solenoid receives an output signal from microprocessor/controller216 it opens, sending pressurized gas to the valves. The valves of thepresent invention remain open as long as pressurized gas flows to thevalve. The gas flow is shut off and the valve closes when the outputdevice controlling the valve receives a close command from themicroprocessor/controller 216.

Turning now to FIG. 5. The microprocessor/controller of the presentinvention can be any programmable microprocessor known to those ofordinary skill in the art that can receive, process, store and relaydata to and from remote sensors and electromechanical devices. Themicroprocessor/controller inputs of the present invention include, butare not limited to, cycle start button 502, cycle abort button 504,treatment timer 506, solvent temperature 508, reset button 510, processlevel sensor 512, high level sensor, solution flow sensor 514, aerationtimer 516, wash timer 518, manual drain key switch 520, process vesselcover sensor, process vessel latch sensor, manual pump forward 522,manual pump reverse 524, manual pump mode 526. The inputs depicted inFIG. 5, and other inputs of microprocessor/controller 500 can includeany number of different options depending on the functions that are tobe automated and conditions to be monitored.

Once data has been received and processed by microprocessor/controller500 output devices responsive to microprocessor/controller 500 controlthe coating system 200 (FIG. 2) and coating process 100 (FIG. 1). Outputdevices of the present invention can be any type known to those ofordinary skill in the art. The output commands used to control thecoating system 200 (FIG. 2) of the present invention include, but arenot limited to, pump motor on/off, pump motor direction valves, holdingvessel out valve, process vessel out valve, low pressure drain gassupply, drain valve open/closed, holding vessel to processing vesselvent, process complete indicator 528, sight glass vent valve, wash fluidon, reset hold signal for treatment timer, circulation cooler/heatercontrol, aeration valve on, main system vent, aeration timer enable,wash timer enable.

The inputs and outputs of the present invention work in a coordinatedfashion to control and monitor the coating system and process of thepresent invention. Table 1 illustrates the coordinated interaction ofthe inputs and outputs of one embodiment of the present invention. It isunderstood that there are many other input/output combinations and thosepresented in Table 1 are not meant to limit the present invention, butmerely to provide one example. The corresponding input and outputabbreviations used in Table 1 are defined in Tables 2 and 3 immediatelyfollowing Table 1.

TABLE I Step Process Step Description Inputs On Outputs On 0 Standby,vessels closed, rest I-3, II-3, II-4 II-2 1 Start cycle, pump to processvessel I-0 mom, I-3, II-3, II-4 I-0, I-1, I-2, I-3, I-6, II-2 2 Processlevel reached, processing I-3, I-5, II-3, II-4 I-1, II-3 3 Process timeelapsed, pumping back to HV I-2, I-7, II-3, II-4 I-0, I-2, I-3, I-6,II-3 4 Back to holding vessel, aeration time on I-2, II-3, II-4 II-0,II-3, II-4, II-5, II-6 5 Aeration done, rinse water fill to level I-2,II-0, II-3, II-4 II-1, II-3, II-5, II-6 6 Full, bubble wash time I-2,I-5, II-0, II-3, II-4 II-3, II-4, II-5, II-6, II-7 7 Dump rinse, blowdown I-2, II-0, II-1, II-3, II-4 I-3, I-4, I-5, II-3, II-6, II-7 8Refill rinse to level I-2, II-0, II-3, II-4 I-5, II-1, II-3, II-5, II-69 Full, 2^(nd) wash cycle I-2, I-5, II-0, II-3, II-4 I-5, II-3, II-4,II-5, II-6, II-7 10 Dump 2^(nd) rinse, blow down I-2, II-0, II-1, II-3,II-4 I-3, I-4, I-5, II-3, II-6, II-7 11 Cycle complete, in process drycycle on I-2, II-0, II-1, II-3, II-4 I-4, I-5, I-7, II-3, II-5, II-6,II-7 12 Process cycle complete, vessel open I-2, II-0, II-1 I-5, I-7,II-3, II-6, II-7 13 Controller reset, cover open, temp low I-4 mom(reset in) I-2 NOTES: Step 2 Input I-3 (Temp Alarm Off) may go offmomentarily due to reaction time of the cold process vessel sensor beingwarmed by the incoming solution. Step 3 Input I-3 (Temp alarm Off) maybe On or Off due to cooling of the Holding Vessel. Controller becomes aHV temp monitor only. Step 4 Inputs I-5 and I-6 (Sightglass Sensors) maybe on due to condensation in the sightlglass during the first minutes ofaeration time.

TABLE II Input No. Description I-0 Start Cycle I-1 Abort Cycle I-2Treatment Timer Time Out I-3 Solution Temp Input I-4 Reset ControllerI-5 Reactor Vessel Process Point Solution Sensor I-6 Reactor Vessel HighSolution Sensor I-7 Solution Flow Switch II-0 Aeration Timer Time OutII-1 Bubble Wash Timer Time Out II-2 Manual Drain Valve On II-3 ProcessVessel Cover Closed II-4 Process Vessel Latched II-5 Manual Pump On(Forward Direction) II-6 Manual Pump On (Reverse Direction) II-7 ManualPump Mode On

TABLE III Output No. Description I-0 Pump Motor On I-1 Pump MotorDirection (ON = Fwr) V¹ 1 & V2 I-2 Holding Vessel Valve On, V5 I-3Process Vessel Valve On, V6 I-4 Low Pressure Drain Air Valve (BlowDown), V10 I-5 Drain Valve On, V4 I-6 Hld. V. to Pro. V. Vent Valve On,V7 I-7 Process Complete Indicator II-0 Sightglass Vent Valve On, V16II-1 Pure Water Valve On, V11 II-2 Reset Treatment Timer II-3 HV Switchfrom Circ. Htr. to Cooler (Rly-2). Circ. Htr. Control to PV. Rly-1 II-4Aeration Valve On, V8 II-5 Roof Vent (Exhaust) Valve, V3 II-6 AerationTimer Enable II-7 Bubble Wash Timer Enable ¹V is an abbreviation forvalve and refers to the pneumatic operated ball valves used in oneembodiment of the present invention.

FIG. 6 depicts compressed gas flow and the gas vents used in oneembodiment of the present invention. Compressed air 600 is provided tocoating system 200 (FIG. 2) through air line 602 when valve 604 isopened. Compressed air then moves through filter 242 and into eitherhigh pressure regulator 236 and through high pressure compressed airvalve 606, or through low pressure regulator 254 and through lowpressure valve 608 to sparger line 610 to provide compressed air tosparger 402 in processing vessel 204.

Coating solution is pumped from holding vessel 202 to processing vessel204 and air is displaced from processing vessel 204 and sight glass 612through sight glass vent valve 614. Sight glass valve 614 opens inresponse to solenoid 616 located in microprocessor/controller 216 (FIG.2) and air is vented out of the system through vent 618 responsive tosolenoid 620. Wash solution is purged from process vessel 204 by closingsight glass vent valve 614 while maintaining air flow into processingvessel 204 through sparger line 610. Air contained in holding vessel 202is released therefrom as the coating solution is pumped from processingvessel 204 through holding vessel 202 to processing vessel vent 622 inresponse to solenoid 624.

FIG. 7 schematically depicts coating solution transfer between holdingvessel 202 and processing vessel 204. Microprocessor/controller 216initiates coating solution transfer following engagement of cycle startbutton 502 (FIG. 5). Solvent transfer pump 702 is activated by solenoid704 and begins pumping coating solution from holding vessel 202 throughholding vessel valve 706 in response to solenoid 708. The coatingsolution is pumped through pump direction valve 708 and directed towardsprocessing vessel 204 by pump direction valve 710. Pump direction valves708 and 710 are responsive to solenoid 714. Coating solution entersprocessing vessel 204 through processing valve 712 that is activated bysolenoid 716. Coating solution returns to holding vessel 202 byreversing its path through pump/direction valve network 226. Drain valve718, responsive to solenoid 720 directs coating solution flow to andfrom processing vessel valve 712, or can be engaged to direct washfluids from processing vessel 204. Manual valve 722 can be engaged todrain spent coating solution from the coating system of the presentinvention and sample port valve 724 can be manually opened to withdrawcoating solution samples for analysis. It is understood that FIG. 7represents one embodiment of the coating solution transfer system of thepresent invention and that many other combinations of pumps and valvesknown to those of ordinary skill in the art can be employed.

Many of the solvents used in association with the coating system of thepresent invention can be toxic and/or flammable. Therefore, the presentinvention has a number of safety features. In one embodiment of thepresent invention a spill containment platform is integrated into thecoating system. The holding vessel, processing vessel, fluid transfersystems, temperature controllers, gas vents and all fluid transfer linesare contained within the perimeter of a tray-like platform having highwall sides. The platform walls are high enough to safely contain theentire combined contents of the holding vessel, the processing vesseland solutions contained within the fluid transfer systems. In theunlikely event that a spill should occur, the manufacturing environmentitself would not be contaminated.

In another embodiment of the present invention the coating system isprovided with a series of fail safe devices composed of sensors thatfeed back to the microprocessor/controller. Sensor locations include,but are not limited to, holding vessel and processing vessel closuresand latches, fluid level minimums and maximums, valves and vents. If themicroprocessor/controller of the present invention does not receive theappropriate inputs from each sensor, the process will either fail to beinitiated or aborted. Moreover, the microprocessor/controller of thepresent invention is provided with a prominent, easily accessible manualoverride that permits the operator to shut the system down should apotentially unsafe condition arise.

EXAMPLES Example 1 Preparation of an Antimicrobial Coating Solution

Transfer 9.06 liters of acetone-free absolute methyl alcohol (cataloguenumber M 1775, Sigma Chemicals, St. Louis, Mo. USA) into the holdingvessel of the present invention and engage the holding vessel mixer.Slowly add 681.3 grams of USP grade Rifampin (Lupin Laboratories, LTD,Mumbai, India) to the methanol. Next, add 568 grams of USP gradeMinocycline (Companhia Industrial Produtora de Antibioticos, S. A.,Castanheira Do Ribatejo, Portugal) to the Rifampin/methyl alcoholmixture. After all of the Rifampin and Minocycline have disolved, slowlyadded 13.63 liters of ACS reagent grade n-butyl acetate (cataloguenumner B 6408 Sigma Chemicals, St. Louis, Mo. USA). Immediately coverthe holding vessel and secure.

Example 2 Exemplary Coating Procedure Including Microprocessor/ContollerInput/Output Sequence

Process Step 0:

Coating System Status: Stand-by condition, process vessel loaded, closedand latched. Vessel temperature 35° C.

Input² Status:

1. Solvent Temperature Alarm off signal from temperature controller. I-3

2. Process Vessel cover closed sensor signal. II-3

3. Process Vessel cover latched sensor signal. II-4

² See Table 2.

Output³ Status:

-   -   1. Treatment Timer reset signal. II-2

³ See Table 3.

Process Step 1

Coating System Status: Initiate process cycle, pumping solution toprocess vessel.

Input Status:

1. Initiate Cycle push button signal (momentary). I-0

2. Solvent Temperature Alarm off signal from temperature controller. I-3

3. Process Vessel cover closed sensor signal. II-3

4. Process Vessel cover latched sensor signal. II-4

Output Status:

1. Solvent Pump On. I-0

2. Pump direction signal out, (pump to process vessel from holdingvessel). I-1

3. Holding Vessel Output Valve Open. I-2

4. Process Vessel Output Valve Open. I-3

5. Holding Vessel to Process Vessel Vent Valve on. I-6

6. Treatment Timer reset signal. I-2

Process Description:

To initiate the process cycle the microprocessor/controller must haveinputs from the temperature controller (solution temperature is atprocess temperature), and the two process vessel cover sensors (coverclosed and latched). Once these inputs are present, the initiate cyclebutton will start the process cycle.

The controller then turns on the solvent pump, the two vessel outputvalves, the vessel to vessel vent valve, and the pump flow directionvalves so the pump direction is from holding vessel to process vessel.

Process Step 2

Coating System Status: Solvent process level reached in process vessel,processing

Input Status:

1. Solvent Temperature Alarm off signal from temperature controller. I-3

2. Process Vessel Solvent Level Sensor signal. I-5

3. Process Vessel cover closed sensor signal. II-3

4. Process Vessel cover latched sensor signal. II-4

Output Status:

1. Pump direction signal out, (pump to process vessel from holdingvessel). I-1

2. Heat control/flow switches to process vessel, stir motor on. Holdingvessel (cool) II-3

Process Description:

When the solution level reaches the sight glass level sensor, a signalis sent to the microprocessor/controller indicating that the processsolution level has been reached. The microprocessor/controller turns offthe pump, the vessel output valves, and the vessel to vessel vent valve,but leaves the pump direction valve in the holding vessel to processvessel position. The microprocessor/controller turns off the resetsignal to the treatment timer allowing the timer to start timing. Themicroprocessor/controller also switches the valves that disconnect thecirculation heater flow from the process holding vessel and maintainsflow to the processing vessel. The microprocessor/controller theninitiates the holding vessel cooling cycle. The magnetic stir unit motoris engaged and the circulation temperature controller switches tomonitor the process vessel temperature.

Process Step 3

Coating System Status: Process time elapsed, pumping solvent back toholding vessel.

Input Status:

1. Cycle Timer Timed Out signal. I-2

2. Solvent Flow Switch Output Signal. I-7

3. Process Vessel cover closed sensor signal. II-3

4 Process Vessel cover latched sensor signal. II-4

Output Status:

1. Solvent Pump On. I-0

2. Holding Vessel Output Valve Open. I-2

3. Process Vessel Output Valve Open. I-3

4. Holding Vessel to Process Vessel Vent Valve On. I-6

5. Circulation heater to process vessel, circulation cooler to holdingvessel. II-3

Process Description:

When the Treatment timer reaches zero, a time-out signal is sent to themicroprocessor/controller. The process vessel stir motor turns off.Circulation heater flows only to the process vessel.

The circulation heater temperature controller begins monitoring anddisplaying the holding vessel temperature. The output signal is openedso the heater element in the circulation heater turns off Themicroprocessor/controller turns on the pump, the vessel output valves,and the vessel to vessel vent valve.

During the first three seconds of pumping, an internalmicroprocessor/controller timer delays the flow switch signal so thepump has time to start solution flow and activate the flow switch. Theflow switch becomes active when the three second timer times out. Whenall of the solution is pumped back into the holding vessel, the pumpstarts pumping air. The flow switch signals themicroprocessor/controller and starts the aeration cycle and timer. Themicroprocessor/controller starts a 10 second pump off delay timer. Thispump off delay purges the air sparger of solvent and allows 10 secondsfor the pump to pump the sparger purge solvent to the holding vessel. Atthe end of the 10 second delay, the controller turns the pump, thevessel output valves, and the vessel to vessel vent valves off

Process Step 4

Coating System Status: Solvent Back to Holding Vessel, Aeration Time.

Input Status:

1. Cycle Timer Timed Out signal. I-2

2. Process Vessel cover closed sensor signal. II-3

3. Process Vessel cover latched sensor signal. II-4

Output Status:

1. Sight lass Vent On. II-0

2. Circulation heater to process vessel, circulation cooler to holdingvessel. II-3

3. Aeration Valve On. II-4

4. Roof Vent Valve On. II-5

5. Aeration Timer Enable. II-6

Process Description:

As stated in the step 3 description, the loss of the flow switch signalcauses the controller to start the aeration cycle. The controller turnson the high flow air valve, the roof vent valve, and the aeration timerenable signal. The aeration timer starts timing. The Sight Glass ventturns on at the end of the pump purge delay time. At the end of thesparger purge 10 second pump off delay, the pump and solution linevalves turn off.

Process Step 5

Coating System Status: Aeration time elapsed, fill process vessel withwash water.

Input Status:

1. Cycle timer timed out signal. I-2

2. Aeration Timer Time Out Signal. II-0

3. Process Vessel cover closed sensor signal. II-3

4. Process Vessel cover latched sensor signal. II-4

Output Status:

1. Pure Water Valve On. II-1

2. Circulation heater to process vessel, circulation cooler to holdingvessel. II-3

3. Roof Vent Exhaust Valve On. II-5

3. Aeration Timer Enable On. II-6

Process Description:

When the aeration timer reaches zero, a signal is sent to themicroprocessor/controller, turning sight glass vent valve off, andturning on the distilled water valve. The vessel fills with pure wateruntil the water level reaches the process level sensor on the sightglass.

Process Step 6

Coating System Status: Process vessel fill of wash water to processlevel, bubble wash on.

Input Status:

1. Cycle Timer Timed Out signal. I-2

2. Process Vessel Process Level Sensor Signal. I-5

3. Aeration Timer Time Out Signal. II-0

4. Process Vessel cover closed sensor signal. II-3

5. Process Vessel cover latched sensor signal. II-4

Output Status:

1. Circulation heater to process vessel, circulation cooler to holdingvessel. II-3

2. Aeration Air Valve On. II-4

3. Roof Vent Exhaust Valve On. II-5

4. Aeration Timer Enable On. II-6

5. Wash Timer Enable Signal. II-7

Process Description:

When the level reached signal from the process level sensor reaches themicroprocessor/controller the water valve is turned off and the washtimer is enabled. The aeration valve, and the roof vent valve remain onto bubble wash the product.

Process Step 7

Coating System Status: Wash Time elapsed, Drain Process Vessel of washwater.

Input Status:

1. Cycle Timer Timed Out signal. I-2

2. Aeration Timer Time Out Signal. II-0

3. Wash Timer Time Out Signal. II-1

4. Process vessel cover closed sensor signal. II-3

5. Process Vessel cover latched sensor signal. II-4

Output Status:

1. Process Vessel Out Valve. I-3

2. Low Pressure Drain Air Valve On. I-4

3. Drain Valve On. I-5

4. Circulation heater to process vessel, circulation cooler to holdingvessel. II-3

5. Aeration Timer Enable On. II-6

6. Wash Timer Enable Signal. II-7

Process Description:

When the wash timer reaches zero, a signal is sent to themicroprocessor/controller. The microprocessor/controller turns off thehigh flow air valve and the roof vent valve, and turns on the lowpressure air valve, process vessel output valve, and drain valve. Lowpressure air blows the wash water to drain. The controller alsoinitiates a five minute interval timer. When the internal timer timesout, the microprocessor/controller turns the low pressure air and thevessel out valve off and activates a one second reset timer that resetsthe wash and drain timers. The three way drain valve remains in thedrain position for the second wash. Process steps 5-7 repeat for asecond wash/drain cycle. The reset timer disables the reset functionafter the first reset so the controller will end the process cycle afterthe second wash/drain cycle.

Process Step 8, Repeat process steps 5, with output I-5 (drain valve)on.

Process Step 9, Repeat process step 6, with output I-5 (drain valve) on.

Process Step 10, Repeat process step 7

Process Step 11

Coating System Status Process Cycle Complete, Dry Cycle On

Input Status:

1. Treatment Timer time Out. I-2

2. Aeration Timer Time Out. II-0

3. Wash Timer Time Out. II-1

4. Process Vessel Closed Signal. II-3

5. Process Vessel Cover Latched Signal. II-4

Output Status:

1. Low Press Drain Air On. I-4

2. Drain Valve. I-5

3. Process Complete Indicator Lamp. I-7

4. Circulation Cooler/Heater Flow Control. II-3

5. Roof Vent On. II-5

6. Aeration Timer Enable. I-6

7. Wash Timer Enable. I-7

Process Description:

With the 1 second Wash/Drain cycle timed out and latched, themicroprocessor/controller does not reset the wash/drain cycle and theprocess is complete. The latched reset timer output turns on the processcomplete lamp at the end of the second wash/drain cycle. The lowpressure drain air remains on and the roof vent opens to dry parts inthe processing vessel.

Process Step 12

Coating System Status: Process Cycle Complete, Process Vessel Open,Remove Product.

Input Status:

1. Treatment Timer Time Out. I-2

2. Aeration Timer Time Out Signal. II-0

3. Wash Timer Time Out Signal. II-1

Output Status:

1. Drain Valve. I-5

2. Process Complete Indicator Lamp On. I-7

3 Circulation heater to processing vessel circulation cooler to holdingvessel. II-3

4. Aeration Timer Enable On. II-6

5. Wash Timer Enable Signal. II-7

Process Description:

Unlatching the process vessel when removing product turns off the roofvent and the low pressure drain.

Process Step 13 Controller Reset

Input Status:

1. Reset Signal (momentary)

Output Status:

1. Reset Signal (Momentary)

Process Description:

The reset signal resets the program to the standby mode. The circulationcooler turns off and is disconnected from the holding vessel.Circulation heater flow switches back to both holding and processingvessels. Process temperature for the next coating process.

From the foregoing description, one skilled in the art can readilyascertain the essential characteristics of the invention and, withoutdeparting from the spirit and scope thereof, can adapt the invention tovarious usages and conditions. Changes in the form and substitution ofequivalents are contemplated as circumstances may suggest or renderexpedient, and although specific terms have been employed herein, theyare intended in a descriptive sense and not for purposes of limitation.Furthermore, any theories attempting to explain the mechanism of actionshave been advanced merely to aid in the understanding of the inventionand are not intended as limitations, the purview of the invention beingdelineated by the following claims.

1. A semi-automated medical device coating system comprising: a firstvessel having a sealable cover, at least one mixing device and at leastone heat transfer device; a second vessel for coating material having asealable cover, at least one mixing device and at least one heattransfer device, said second vessel in two-way fluid communication withsaid first vessel; a fluid transfer system adapted to transfer fluidsbetween said first and said second vessels; a support adapted to suspenda device in said second vessel; and a gas operated sparger in saidsecond vessel adapted to transfer gas from an external gas supply intosaid second vessel.
 2. The semi-automated medical device coating systemof claim 1 wherein said coating system is a closed system substantiallypreventing exposure of said fluid to the ambient atmosphere or light. 3.The semi-automated medial device coating system of claim 1 furthercomprising a plurality of sensors cooperatively connected to said firstvessel, said second vessel, said fluid transfer system, said heattransfer devices and said mixers, said sensors responsive to at leastone microprocessor/controller.
 4. The semi-automated medical devicecoating system of claim 1 further comprising at least one temperaturecontroller responsive to at least one microprocessor/controller forheating and cooling said heat transfer device of said first and saidsecond vessels.
 5. The semi-automated medical device coating system ofclaim 1 wherein said fluid transfer system is at least one pump.
 6. Thesemi-automated medical device coating system of claim 1 wherein saidsparger is a spiral shaped device located within said second vessel. 7.A semi-automated implantable medical device coating system comprising: acontainment platform having at least one temperature controller; aholding vessel fixed to said containment platform having a firstsealable closure, at least one mixer and a first heat transfer device incooperation with said at least one temperature controller; a processingvessel for coating material said processing vessel fixed to saidcontainment platform having a second sealable closure, a gas sparger, atleast one mixer, a support for suspending said implantable medicaldevice within said processing vessel and a second heat transfer devicein cooperation with said at least one temperature controller; a firstfluid transfer system in cooperation with said containment platformadapted to transfer fluids between said holding vessel and saidprocessing vessel; a second fluid transfer system in cooperation withsaid containment platform adapted to transfer fluid between saidprocessing vessel and a remote fluid reservoir and a waste reservoir; agas reservoir in cooperation with said gas sparger; a plurality ofvalves in cooperation with said first and said second fluid transfersystems and said gas reservoir; a plurality of sensors in cooperationwith said holding vessel, said processing vessel, said first and saidsecond sealable closures, said first and said second heat transferdevices, said first and said second fluid transfer systems, saidplurality of valves and said at least one temperature controller; aprogrammable controller responsive to said plurality of sensors.
 8. Thesemi-automated implantable medical device coating system of claim 7wherein said programmable controller is adapted to regulate thecontents, temperatures, fluid levels, and gas flow within said holdingvessel and said processing vessel.
 9. The semi-automated implantablemedical device coating system of claim 7 wherein said programmablecontroller is adapted to open and close said plurality of valves. 10.The semi-automated implantable medical device coating system of claim 7wherein said programmable controller is adapted to act as a fail-safemonitor responsive to said plurality of sensors.
 11. A semi-automatedmedical device coating system comprising: a coating solution holdingvessel; a processing vessel for coating medical devices separate formsaid coating solution vessel; a coating solution transfer system; a heattransfer system for heating and cooling said holding vessel and saidprocessing vessel either simultaneously or separately; a mixerassociated with said holding vessel and said mixing vessel; at least oneremote sensor; at least one microprocessor/controller for receiving datafrom said at least one remote sensor and for transmitting information tosaid coating solution transfer system and said heat transfer system; aproduct suspension device for holding said medical device in placeduring coating, a wash solution reservoir; a wash solution transfersystem; at least one valve; and at least one vent.
 12. A medical devicecoating system comprising: a first receptacle, said receptacle comprisedof a material capable of holding an antimicrobial substance withoutintroducing contamination; an antimicrobial substance received initiallyin said first receptacle a second receptacle in fluid communication withsaid first receptacle; said fluid communication being substantiallyclosed to ambient air at least during flow of fluid; said secondreceptacle sized and shaped to receive at least one medical device; andan electronic controller to govern flow between said first receptacleand said second receptacle wherein the antimicrobial substance is coatedand remains on the at least one medical device when the at least onemedical device is received in the second receptacle.
 13. A medicaldevice coating system comprising: a first receptacle, said receptaclecomprised of a material capable of holding an antimicrobial substancewithout introducing contamination; an antimicrobial substance receivedinitially in said first receptacle; a second receptacle in fluidcommunication with said first receptacle; said fluid communication beingsubstantially closed to ambient air at least during flow of fluid; saidfirst receptacle and said second receptacle being continually maintainedunder an inert gas; said second receptacle sized and shaped to receiveat least one medical device; and an electronic controller to govern flowbetween said first receptacle and said second receptacle wherein theantimicrobial substance is coated and remains on the at least onemedical device when the at least one medical device is received in thesecond receptacle.